Insulin Resistance and Cardiometabolic Impacts

manaf, asman (2010) Insulin Resistance and Cardiometabolic Impacts. (Unpublished)

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Abstract

It has been well characterized four major molecular signaling mechanisms activated by hyperglycemia in endothelial cells and other cell types vulnerable to hyperglycemic injury. These include activation of protein kinase C ( PKC ) via diacylglycerol, increased hexosamine pathway flux, increased advanced glycation end products ( AGEs ) formation, and increased polyol pathway flux. It has been recently suggested that excessive mitochondrial production of reactive oxygen species ( ROS ), specifically superoxide, will be a common unifying mechanism that integrates the above pathways. The phenomenon of adverse effects of hyperglycemia on insulin target tissue and on pancreatic β cells has been termed “glucotoxicity”. The DCCT ( Diabetes Control and Complication Trial ) and the UKPDS ( United Kingdom Prospective Diabetes Study ) established that hyperglycemia is the initiating cause of the diabetic tissue damage. The new paradigm of a unifying mechanism for the progress and pathogenesis of diabetic complication, may be useful in getting novel approaches for the prevention and treatment of diabetes. So, the bad regulation of diabetes is believed as the main accelerating factor in this process although genetic determinants and many independent factors, such as metabolic syndrome may be involved. Thiazolidinedione, an insulin sensitizer, is one of potent oral antihyperglycemic agents and anti cardiometabolic effects for diabetes. Keywords: hyperglycemia, glucotoxicity, diabetic progress, thiazolidinediones.

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